| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with active psoriatic arthiritis |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10037161 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of infliximab plus methotrexate versus methotrexate alone in methotrexate naïve subjects with active, polyarticular PsA who have had inadequate response to standard of care treatment. The primary objective is the proportion of patients with an ACR20 improvement at week 16 from baseline. |
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| E.2.2 | Secondary objectives of the trial |
• Proportion of subjects with ACR50, 70 improvement from baseline at weeks 2, 6, 14, and 16
• PASI75 improvement
• Proportion of subjects with DAS28 improvement from baseline at weeks 2, 6, 14, and 16
• The change in each of the ACR20 domains. This includes the number of swollen and tender joints, subject’s assessment of pain, subject’s global assessment of disease activity, evaluator’s global assessment of disease activity and CRP.
• The change in the number of digits with dactylitis.
• To evaluate improvement of enthesitis using MASES
• The change in Fatigue and the duration of morning stiffness.
• The change in ESR.
• The change in the disability index of the Health Assessment Questionnaire.
• Development of ANA or anti dsDNA
• Safety
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
The subject must meet ALL of the criteria listed below for entry into the study:
1) Subject must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
2) Subject aged 18 years or more, of either sex and any race
3) Diagnosis of Psoriatic Arthritis with peripheral polyarticular involvement.
Patients will have at least one of the following:
i. DIP involvement
ii. polyarticular arthritis, absence of rheumatoid nodules and presence of psoriasis
iii. arthritis mutilans
iv. asymmetric peripheral arthritis
4) Negative rheumatoid factor
5) The disease should have been diagnosed at least 3 months prior to screening.
6) Active disease at the time of screening and prior to receiving the baseline study medication(s) as defined by:
i. 5 or more swollen joints and
ii. 5 or more tender joints
iii. and one out of the following three categories:
• ESR ≥ 28 mm/h
• CRP ≥ 15 mg/l
• Morning stiffness ≥ 45 min
7) Subjects must confirm that they are practicing adequate contraception:
Female subjects of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active during the study) must agree to use a medically accepted method of contraception or be surgically sterilized prior to screening, while receiving protocol-specified medication, and for 6 months after stopping the medication.
Acceptable methods of contraception include condoms (male and female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD, oral or injectable hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation).
8) Female subjects of childbearing potential must have a negative pregnancy test at Screening.
9) Subjects must be eligible for anti-TNF treatment according to applicable local guidelines. For all patients chest X-ray and skin test results must be available at baseline.
10) If using NSAIDs or corticosteroids other than i.v., i.m. or i.a. the patient must be on a stable dose for two weeks prior screening (maximum dose up to 10 mg/day of prednisone, or its oral equivalent).
11) The screening laboratory tests must meet the following criteria:
i. Hemoglobin ≥ 10 g/dl providing the low hemoglobin level is not due to other diseases than anemia of chronic inflammation.
ii. WBC ≥ 3500 / µl
iii. Neutrophils ≥ 1500 / µl
iv. Platelets ≥ 100 000 / µl
v. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase ≤1.5 x upper limit of normal
vi. Total bilirubin ≤ 1 x upper limit of normal
vii. Serum creatinine ≤ 1.5 mg/dl
12) Patient must be able to adhere to the study visit schedule and other protocol requirements and must have given informed consent prior to any screening procedures.
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|
| E.4 | Principal exclusion criteria |
The subject will be excluded from entry into the study if ANY of the criteria listed below are met.
1) Subject is a female who is pregnant, intends to become pregnant during the study (or within 6 months after study completion), or nursing.
2) Patients with other inflammatory diseases that might interfere with the evaluation of the psoriatic arthritis.
3) Previous treatment with Infliximab
4) Subjects who have previously received MTX or have not discontinued their other DMARD therapy (i.e. sulfasalazine, hydroxychloroquine, leflunomide).
5) Patients with fibromyalgia syndrome.
6) Use of cyclosporine or tacrolimus within 4 weeks prior to screening. Use of IM, IV, or IA corticosteroids within 4 weeks prior to screening.
7) Treatment with any investigational drug within 3 months prior to screening.
8) Previous treatment with a monoclonal antibody or a fusion protein.
9) A history of known allergy to murine proteins.
10) History of infected joint prosthesis within the previous 5 years.
11) Chronic infections.
12) History of active tuberculosis requiring treatment within previous 3 years, or history of opportunistic infections within 2 months, uncontrolled active infection or documented HIV infection. Also excluded are patients with evidence of latent tuberculosis and patients with old tuberculosis without documented adequate therapy if they will not be treated according to local TB guidelines.
13) Subject has any clinically significant deviation from normal in the physical examination, Chest X-ray, or ECG that, in the investigator’s judgment, may interfere with the study evaluation or affect subject safety.
14) Current signs or symptoms of other severe uncontrolled diseases which in the investigators opinion would put the patient at an unacceptable risk.
15) History of lymphoproliferative disease, any current malignancies or history of malignancy within 5 years other than successfully treated basal cell carcinoma or squamous cell carcinoma of the skin.
16) Subject is part of the staff or a family member of the staff personnel directly involved with this study.
17) History of drug abuse.
18) Subjects who are participating in any other clinical study.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint of the study, at end of study treatments, is the ACR preliminary definition of improvement from baseline to week 16, as defined as:
• ≥ 20 % improvement in
- swollen joint count and tender joint count
• and ≥ 20% improvement in 3 of following 5 assessments:
- patient’s assessment of pain (VAS)
- patient’s global assessment of disease activity (VAS)
- evaluator’s global assessment of disease activity (VAS)
- HAQ
- CRP
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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